Studies of the molecular changes that are a consequence of various disease states may ultimately lead to an understanding of the process of disease development and possible prevention of the progression of disease. We are developing cDNA microarray technology and intend to use this technology to determine mechanisms of apoptosis. Advances in genomics has allowed for the development of technology where gene expression of thousands of genes may be monitored simultaneously in biological samples. We are investigating mechanisms that lead to cell apoptosis following exposure to a variety of agents using cDNA microarrays. HIV infection leads to the disease AIDS, that is characterized by loss of immune cells. The precise mechanism by which HIV replication leads to cell killing is not known. This is likely linked however to cellular events including an increase in the level of tumor necrosis-alpha. The power of cDNA microarray technology will allow us to observe genomic consequences of response to apoptotic agents. These basic studies will contribute information that may be useful in the treatment and understanding of some diseases including AIDS and cancer where apoptosis is a significant contributing component. This technology should elucidate new pathways or molecules involved in this process. Further understanding of the mechanisms of tumor necrosis factor on apoptosis may lead to new therapies that may block HIV-mediated cell killing and should also lead to the identification of new genes/targets involved in environmental, viral or genetic-linked diseases including cancer and diseases of the immune, nervous, and pulmonary/respiratory systems.